Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
Article has an altmetric score of 3

See more details

Referenced in 1 patents
63 readers on Mendeley
  • Article usage
  • Citations to this article (207)

Advertisement

Research Article Free access | 10.1172/JCI4394

Hypotension and reduced nitric oxide-elicited vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase.

Y Ohashi, S Kawashima, K i Hirata, T Yamashita, T Ishida, N Inoue, T Sakoda, H Kurihara, Y Yazaki, and M Yokoyama

The First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.

Find articles by Ohashi, Y. in: JCI | PubMed | Google Scholar

The First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.

Find articles by Kawashima, S. in: JCI | PubMed | Google Scholar

The First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.

Find articles by Hirata, K. in: JCI | PubMed | Google Scholar

The First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.

Find articles by Yamashita, T. in: JCI | PubMed | Google Scholar

The First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.

Find articles by Ishida, T. in: JCI | PubMed | Google Scholar

The First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.

Find articles by Inoue, N. in: JCI | PubMed | Google Scholar

The First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.

Find articles by Sakoda, T. in: JCI | PubMed | Google Scholar

The First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.

Find articles by Kurihara, H. in: JCI | PubMed | Google Scholar

The First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.

Find articles by Yazaki, Y. in: JCI | PubMed | Google Scholar

The First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.

Find articles by Yokoyama, M. in: JCI | PubMed | Google Scholar

Published December 15, 1998 - More info

Published in Volume 102, Issue 12 on December 15, 1998
J Clin Invest. 1998;102(12):2061–2071. https://doi.org/10.1172/JCI4394.
© 1998 The American Society for Clinical Investigation
Published December 15, 1998 - Version history
View PDF
Abstract

Nitric oxide (NO), constitutively produced by endothelial nitric oxide synthase (eNOS), plays a major role in the regulation of blood pressure and vascular tone. We generated transgenic mice overexpressing bovine eNOS in the vascular wall using murine preproendothelin-1 promoter. In transgenic lineages with three to eight transgene copies, bovine eNOS-specific mRNA, protein expression in the particulate fractions, and calcium-dependent NOS activity were confirmed by RNase protection assay, immunoblotting, and L-arginine/citrulline conversion. Immunohistochemical studies revealed that eNOS protein was predominantly localized in the endothelial cells of aorta, heart, and lung. Blood pressure was significantly lower in eNOS-overexpressing mice than in control littermates. In the transgenic aorta, basal NO release (estimated by Nomega-nitro-L-arginine-induced facilitation of the contraction by prostaglandin F2alpha) and basal cGMP levels (measured by enzyme immunoassay) were significantly increased. In contrast, relaxations of transgenic aorta in response to acetylcholine and sodium nitroprusside were significantly attenuated, and the reduced vascular reactivity was associated with reduced response of cGMP elevation to these agents as compared with control aortas. Thus, our novel mouse model of chronic eNOS overexpression demonstrates that, in addition to the essential role of eNOS in blood pressure regulation, tonic NO release by eNOS in the endothelium induces the reduced vascular reactivity to NO-mediated vasodilators, providing several insights into the pathogenesis of nitrate tolerance.

Version history
  • Version 1 (December 15, 1998): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Related comments

  • "Endothelial NOS and dietary L-arginine supplementation"
    David Gurwitz

Metrics

Article has an altmetric score of 3
  • Article usage
  • Citations to this article (207)

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 1 patents
63 readers on Mendeley
See more details